Diagnostic accuracy of 99Tcm-HIDA with cholecystokinin and gallbladder ejection fraction in acalculous gallbladder disease

The diagnostic accuracy and clinical impact of 99Tcm hepatic iminodiacetic acid (HIDA) imaging with cholecystokinin (CCK) was investigated in a prospective study of 359 patients over an 11 year period. All patients presented with right upper quadrant biliary type pain and had a normal ultrasound investigation prior to imaging. CCK was administered as a 3 min infusion at peak gallbladder uptake of HIDA. A gallbladder ejection fraction (GBEF) was used to quantify the gallbladder response to CCK. Two hundred and forty-four of 359 (68%) patients had an abnormal GBEF (< or = 35%). One hundred and thirty-four of 141 (95%) patients who underwent cholecystectomy had abnormal surgical/histological findings and/or relief of symptoms on long-term (mean 5.7 years) follow-up. Clinical follow-up, mean of 5.9 years, of the patients with GBEF > 35% showed 73/79 (92%) of them with little evidence of gallbladder disease. For a total 261 patients with mean clinical follow-up of 5.7 years the sensitivity of GBEF measurement is 95%, specificity is 92% and overall accuracy is 94%. It is concluded that 99Tcm-HIDA imaging, with a 3 min infusion of CCK, is a highly accurate technique and valuable in the diagnostic management of patients with suspected acalculous gallbladder disease.     

Functional hepatobiliary disease: chronic acalculous gallbladder and chronic acalculous biliary disease

Chronic acalculous gallbladder and chronic acalculous biliary disease are considered functional hepatobiliary diseases. Cholescintigraphy provides physiologic imaging of biliary drainage, making it ideally suited for their noninvasive diagnosis. For chronic acalculous gallbladder disease, calculation of a gallbladder ejection fraction during sincalide cholescintigraphy can confirm the clinical diagnosis and has become a common routine procedure in many nuclear medicine clinics. Published data generally confirm a high overall accuracy for predicting relief of symptoms with cholecystectomy. However, data also exist suggesting it is not useful. The discrepant results probably are caused by the various different methodologies that have been used for sincalide infusion. Proper methodology of sincalide infusion is critical for providing accurate reproducible results, minimizing false positive studies, and preventing adverse side effects. The most common causes for the postcholecystectomy pain syndrome are partial biliary obstruction secondary to stones or tumor and sphincter of Oddi dysfunction. The latter is a partial biliary obstruction at the level of the sphincter. This has long been considered a functional hepatobiliary disease because of the lack of anatomical abnormalities. Sphincterotomy is the present treatment; however, diagnosis requires invasive procedures, such as endoscopic retrograde cholangiopancreatography and sphincter of Oddi manometry, which has a high complication rate and is not widely available. The unique ability of cholescintigraphy to image biliary drainage allows noninvasive diagnosis. Different methodologies have been reported, many with good overall accuracy. Various pharmacologic interventions and quantitative methodologies have been used in conjunction with cholescintigraphy to enhance its diagnostic capability. Further investigations are needed determine the optimal methodology; however, cholescintigraphic methods have already a clinical role in the diagnosis of sphincter of Oddi dysfunction and will be used increasingly in the future.     

Comparison of fatty meal and intravenous cholecystokinin infusion for gallbladder ejection fraction.

Gallbladder ejection fraction (GBEF) measured with a fatty meal (half-and-half milk) was compared with that measured with 2 equal sequential intravenous infusions of cholecystokinin (CCK-8) in a paired study of healthy subjects. METHODS: GBEF was measured by (99m)Tc-hepatic iminodiacetic acid cholescintigraphy in 13 healthy subjects. Each subject received 2 sequential doses of CCK-8 (3 ng/kg/min for 10 min) on day 1, followed by, on day 2, a 240-mL (8 oz) fatty meal (half-and-half milk) per 70 kg of body weight. RESULTS: The mean +/- SD GBEF of 53.6% +/- 20.2% with fatty meal was significantly lower than the mean of 75.8% +/- 16.3% (P < 0.01) with the first dose of CCK-8 and 71.3% +/- 17.4% (P < 0.05) with the second dose. Fatty meal GBEF varied widely, from 23.5% to 91.8%. Percentile rankings of the fatty meal GBEF were determined as the preferred methodology for reporting results. Latent and ejection periods were significantly longer with fatty meal than with either dose of CCK-8. CONCLUSION: GBEF measured with fatty meal can serve as an alternative method to intravenous injection of CCK-8 when the hormone is no longer available for clinical use. The measurement of GBEF with fatty meal requires careful attention to the details of the meal and the measurement time sequence.     

Normal gallbladder ejection fraction after morphine augmentation.

PURPOSE: Morphine sulfate causes spasm of the sphincter of Oddi. Conversely, the cholecystagogue sincalide produces relaxation of the sphincter and contraction of the gallbladder. This prospective study evaluated whether sincalide could produce normal gallbladder emptying after low-dose morphine sulfate (0.04 mg/kg). METHODS: Thirty to 120 minutes (mean, 51 minutes) after morphine sulfate-augmented gallbladder visualization, 25 gallbladder ejection fractions in 24 patients were measured. One patient was studied twice, 2 weeks apart. Gallbladder ejection fractions were calculated after controlled 30-minute infusions of sincalide (0.02 microg/kg). RESULTS: Fourteen gallbladder ejection fractions were normal (mean, 63%; range, 45% to 80%) and 11 gallbladder ejection fractions were abnormal (mean, 12%; range, 5% to 19%; P < 0.001). CONCLUSIONS: Normal gallbladder ejection fractions can be obtained as early as 30 minutes after administration of low-dose morphine sulfate. Potential applications of post-morphine sulfate sincalide challenge would include, for example, to support true-negative morphine sulfate-augmented gallbladder visualization in a patient with a high clinically indicated potential of having acute cholecystitis.     

Automated calculation of gallbladder ejection fraction

We have developed a computer method which by automatically locating the border of the gallbladder in each image and subtracting a varying location-dependent background corresponding to the gallbladder border overcomes the difficulties associated with quantitating gallbladder contraction. These difficulties are attributable to significant and changing background activity, imprecise manual delineation of the gallbladder, and the changing position and shape of the gallbladder. Validation studies using a gallbladder phantom showed the method to be very accurate. No significant difference (P greater than 0.05) was observed between the expected and calculated ejection fractions. Ten patient studies were analyzed, with a resulting range of gallbladder ejection fractions of 22-79%. Excellent reproducibility was obtained with an average intraobserver coefficient of variation of 3.5%, and no statistically significant difference in interobserver measurements (P greater than 0.05). The regression line for interobserver measurements had a slope of 0.96 +/- 0.08, an intercept of 1.6 +/- 4.0%, and a correlation coefficient of 0.99. From these preliminary results we conclude that this method offers a reliable means of quantitating gallbladder contraction.     

Is gall bladder ejection fraction a reliable predictor of acalculous gall bladder disease?

The use of quantitative 99Tcm-EHIDA imaging with cholecystokinin and the measurement of gall bladder ejection fraction in a prospective study of 89 patients with right upper quadrant pain is described. Correlation with surgical and histological findings and clinical follow-up suggests that gall bladder ejection fraction < or = 35% is a reliable and accurate indicator of acalculous gall bladder disease.     

Chronic acalculous gallbladder disease: multiimaging evaluation with clinical-pathologic correlation

Despite the recent advances in hepatobiliary imaging, the diagnosis of chronic acalculous gallbladder disease remains difficult. A retrospective study was undertaken to assess the value of a multiimaging approach in detecting chronic acalculous gallbladder disease and in predicting which patients would obtain symptomatic relief after cholecystectomy. Of 199 patients with chronic cholecystitis, 26 (13%) had no gallstones. Of these 26, only 17 (65%) had symptoms related to chronic cholecystitis; in the remainder, the histologic diagnosis was made incidentally. After cholecystectomy, 13 (76%) of the 17 symptomatic patients obtained long-term symptomatic relief, while in four, the symptoms recurred. Among patients with histologic changes of chronic cholecystitis, biliary scintigraphy was the most sensitive technique (sensitivity, 89%). The sensitivity of sonography and oral cholecystography was 61.5% and 66%, respectively. However, for identifying symptomatic patients who may obtain long-term symptomatic relief after cholecystectomy, the accuracy of sonography, oral cholecystography, and biliary scintigraphy was 82%, 86%, and 38%, respectively. When two tests were in agreement the accuracy was 88%. For chronic acalculous cholecystitis, more than one study must be performed in order to make the correct diagnosis and to predict good results from cholecystectomy.     

Cholecystokinin cholescintigraphy: detection of abnormal gallbladder motor function in patients with chronic acalculous gallbladder disease

CCK cholescintigrams were performed in 374 patients with recurrent postprandial right upper quadrant pain, biliary colic, and a normal gallbladder sonogram and/or cholecystogram. The results of these examinations were correlated with the patients' final medical/surgical diagnoses. Twenty-seven patients recruited as control volunteers without objective clinical evidence of biliary disease also underwent CCK cholescintigraphy to determine if the degree of gallbladder contraction post-CCK differs in symptomatic versus asymptomatic subjects. Decreased gallbladder motor function was identified (maximal gallbladder ejection fraction response to CCK less than 35%) in 94% of patients with histopathologically confirmed chronic acalculous cholecystitis or the cystic duct syndrome and in 88% of patients clinically believed to have chronic acalculous biliary disease. Decreased gallbladder motor function does not distinguish symptomatic from asymptomatic gallbladder disease.     

Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy.

PURPOSE: To evaluate the utility of magnetic resonance cholangiography (MRC) in estimation of gallbladder ejection fraction (GBEF) and to comparing this value to the conventional method, hepatobiliary scintigraphy (HBS). MATERIALS AND METHODS: Twenty-one healthy volunteers were imaged on sequential weeks to determine GBEF using MRC and HBS. GBEF was calculated by HBS after infusion of 20 ng/kg of sincalide following injection of 111 Mbq of Tc 99(m) mebrofenin. For estimation by MRC, imaging of the gallbladder was performed before and after slow infusion of sincalide every 5 minutes, for a total of 60 minutes. Gallbladder imaging was performed using a heavily T2-weighted 2D fast spin echo (FSE) sequence. Data was analyzed using a variance component analysis technique. RESULTS: Mean GBEF by HBS was 65.7%, with an SD of +/-27.3%. Mean GBEF by MRC was 62.7%, with an SD of +/- 20.4%. If minimum normal GBEF is set at 35%, two of the cases showed discordance, with HBS calculating an abnormally low average GBEF compared to MRC. Additionally, two cases showed abnormally low GBEF for both modalities. The coefficient of correlation between HBS and MRC was 0.72. Inter- and intraobserver variance is acceptable within the two modalities with <1.1% variation. CONCLUSION: GBEF can be calculated with MRC, yielding similar values when a group of volunteers are considered. Further study with symptomatic patients is needed to determine the validity of this technique for clinical diagnosis.     

Right and left ventricular ejection fraction evaluation in patients with chronic pulmonary disease. Comparison of nuclear medicine methods

Our aim was to evaluate right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF) in patients with chronic pulmonary disease (CPD) during a standard 99mTc-isonitrilium myocardial perfusion study. Forty patients (14 women and 26 men, mean age 67.7 +/- 7 years old) suffering from CPD enrolled in this study. Patients were consecutively submitted to: a) First pass (FP) angiocardiography with 99mTc (Tauc-FP). b) Multigated angiocardiography (MUGA). c) FP with 99mTc-sestamibi (MIBI-FP). d) Gated FP (MIBI-gFP) and GatedSPECT was performed in 23 patients. A simple SPECT study was performed to the rest of them. Our results showed: For the RV: RVEF measured by each method: Tauc-FP =49.09+/-8.4%, MUGA =48.51+/-10.6%, MIBI-FP =49.45+/-7.8 % and MIBI-gFP =52.49+/-6.05%. No difference among these methods was noted (P=0.674). MIBI-FP ejection fraction range was wider than MIBI-gFP and narrower than MUGA. A strong correlation (r=0.88 P<0.01) and good agreement was found between MIBI-gFP and MIBI-FP. Less strong correlation was estimated between not only Tc-FP and MUGA (r=0.76 P<0.01) but MIBI-FP and MUGA (r=0.68 P<0.01) as well with no sufficient agreement. For the LV: LVEF was also measured by each method: Tauc-FP=61,1+/-8,5%, MUGA=61,2+/-10%, MIBI-FP=61,8+/-6%,EF GSPECT=60,2+/-7%. There was a strong correlation (r=0.87 P<0.01) with good agreement between Tauc-FP and MUGA. For all patients, correlation between MIBI-FP and GSPECT was weak (r=0.62 P<0.01) but ameliorated by the exclusion of 4 patients with small end diastolic volumes (EDV) (r=0.82 P<0.01). The correlation between MUGA and GSPECT got stronger (r=0.85 P<0.01) by the same exclusion. Finally, a strong correlation (r=0.81 P<0.01) with sufficient agreement was noted between MIBI-FP and MUGA. IN CONCLUSION: For the RV: simple or gated FP are reliable with good agreement methods of RVEF evaluation in patients with CPD that can easily be performed during every radionuclide isonitrilium myocardial perfusion study. MUGA is proved to be comparative to the FP estimation of RV EF. The gFP affords the narrowest range of RVEF calculated, allowing the more accurate functional identification of RV borders. For the LV: FP (with 99mTc or with sestamibi-99mTc) is a reliable method of LVEF measurement in patients with CPD when compared with MUGA. MuIotaBetaIota-FP can evaluate LVEF during a standard myocardial perfusion study with radionuclide isonitrilium. GSPECT-EF correlation with EF measured by MUGA or FP is strongly affected by EDV.     

Scintigraphic gallbladder visualization with gangrenous acalculous cholecystitis

Hepatobiliary scintigraphy evaluates the biliary clearance of Tc-99m-labeled iminodiacetic acid agents (Tc-99m IDA) and has a high sensitivity and specificity for the diagnosis of acute cholecystitis. False-negative studies are extremely rare. We describe an apparently normal nonmorphine-augmented hepatobiliary study in gangrenous acalculous cholecystitis. Based on clinical findings, computed tomography, and ultrasound demonstration of a dilated gallbladder, a cholecystectomy was performed. Pathologic examination of the gallbladder revealed acute gangrenous cholecystitis with culture positive for Klebsiella pneumoniae.     

Constancy and variability of gallbladder ejection fraction: impact on diagnosis and therapy.

The main objective of this study was to test the constancy and variability of gallbladder (GB) ejection fraction (EF) in long-term studies to (a) determine whether EF ever becomes normal once it is low, (b) determine how long it takes for the EF to become abnormal once it is found to be normal, (c) explore the cause of low EF, and (d) define objective parameters for biliary and nonbiliary abdominal pain. METHODS: Fifty-two patients (42 women, 10 men) who underwent quantitative cholescintigraphy twice (total studies, 104), over a mean period of 38.54 mo between studies, were chosen for retrospective analysis. They were divided into the following groups: control (n = 13; nonbiliary abdominal pain), chronic acalculous cholecystitis (CAC) (n = 27; biliary abdominal pain), chronic calculous cholecystitis (CCC) (n = 6; biliary abdominal pain), and opioid (n = 6; nonbiliary abdominal pain). The last group had received an opioid before cholecystokinin-8 (CCK-8) infusion in one study but not in the other study. A GBEF value of > or =35% was considered normal with a 3-min infusion and > or =50% as normal with a 10-min infusion of CCK-8. RESULTS: The mean GBEF value was reproducible between the 2 sequential studies in the control group (66.0% +/- 20.5% vs. 73.9% +/- 17.7%), CAC group (24.4% +/- 22.3% vs. 16.9% +/- 10.9%), and CCC group (20.8% +/- 20.9% vs. 27.5% +/- 34.5%) but not in the opioid group (14.8% +/- 14.6% vs. 56.5% +/- 31.7%). The severity of GBEF reduction in CAC increased with time: 7.2% +/- 8.1% within 12 mo, 16.1% +/- 14.9% in 13-47 mo, and 23.5% +/- 21.3% in 48-168 mo. None of the 27 patients with CAC developed a gallstone as detected by ultrasound during the study period. In 5 patients with CAC, a mean period of 52.6 +/- 28.9 mo was required for conversion from normal to a low EF. CCK-induced cystic duct spasm is the etiology for low EF in both CAC and CCC. CONCLUSION: Normal and low GBEF values are reproducible in long-term studies. Once the EF reaches a low value, it does not return to normal, and a normal value requires many years to become abnormal. CCK-induced cystic duct spasm is the cause of low GBEF in CAC and CCC, and the severity of EF reduction is similar for both. Exclusion of opioid intake immediately before the study is critical before attributing a low GBEF value to an irreversible GB motor dysfunction.     

An audit of biliary scintigraphy in a district general hospital (1993-1998) with special reference to the investigation of acalculous gallbladder disease

One hundred and ninety nine cholescintigrams were performed at our hospital between January 1993 and December 1998. Of these, 96 were performed as part of the investigation of right upper quadrant or epigastric pain in patients whose prior biliary ultrasound scans had shown no abnormalities. In this group of patients, 60 cholescintigrams were reported as normal, 28 as abnormal and eight as equivocal. A review of the case notes for this group was made, with 91 out of 96 case notes being retrieved. Thirteen of the 58 (22%) patients with normal cholescintigrams either underwent or had been offered cholecystectomy, compared with 22 of the 27 (81%) with 'definitely abnormal' cholescintigrams. Of the subset of patients with abnormal cholescintigrams subsequently undergoing cholecystectomy, 16 out of 18 were found to have histologically abnormal gallbladders, while 11 out of 18 reportedly had their symptoms cured or improved. A fatty meal is used in our unit as the stimulus to gallbladder contraction, in contrast to the majority of papers published in the literature. We believe that the use of a fatty meal is acceptable and that the use of intravenous exogenous cholecystokinin is probably best reserved for the small group of patients with equivocal scintigrams who may require further investigation.     

Comparison of left ventricular ejection fraction and regional contractility fraction pre and post coronary angiography.

Thirty patients [four normals, eight with mild and 18 with severe coronary artery disease (CAD)] were studied to evaluate left ventricular function type and post coronary angiography. The end diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF) and the regional contractility fractions (RCF) of eight ventricular segments were evaluated by left ventriculography. The RCF's were analyzed, in addition to the EF's to ascertain the effect of contrast material upon normal and scarred or ischemic segments of the left ventricle, and to rule out spurious findings in the EF due to coexistent reciprocal changes in RCF's. There was good correlation (r = .45 to .97 and p less than .01 to less than .001) in the above parameters of left ventricular function in patients with and without CAD before and after angiography. Thus, although intraventricular and intracoronary injections of contrast material produce transient changes in myocardial contractility, in a clinical setting left ventriculography may be performed prior to or following coronary angiography without danger of spurious results in normals and in patients with CAD.     

Effect of sequential administration of an opioid and cholecystokinin on gallbladder ejection fraction: brief communication.

This study was undertaken to test the effect of sequential administration of an opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction. METHODS: Forty-nine patients who had received an opioid underwent quantitative cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal state, more of the hepatic bile entered the gallbladder (67%) than the small intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in 37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted in 7 patients, but only one showed paradoxical filling of greater than 20% and none had a normal gallbladder ejection fraction. The lowering effect of opioids on gallbladder ejection fraction may last as long as 18 h after intake. CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of patients who had received an opioid and thus could exclude both acute and chronic cholecystitis during a single hepatobiliary study.     

Detection of acalculous gallbladder disease using Tc99m EHIDA imaging and cholecystokinin

The use of Tc^99m ethyl hepatic iminodiacetic acid (EHIDA) imaging with cholecystokinin (CCK) in a prospective study of 115 patients with right upper quadrant biliary-type pain is described. All patients had normal US, oral cholecystography and/or endoscopy investigations. A 2-min infusion of CCK was administered at peak gallbladder uptake of EHIDA. A gallbladder ejection fraction (CBEF) was used to quantify the gallbladder response to CCK. A total of 79 of 115 patients (69%) had an abnormal GBEF ( 35%). Of 43 patients who underwent cholecystectomy 42 (97%) had abnormal surgical/histological findings and/or complete long-term relief of symptoms. It was concluded that Tc^99m EHIDA imaging, with a 2-min infusion of CCK and a measured GBEF 35%, is highly predictive of acalculous gallbladder disease and a favourable outcome following cholecystectomy. Correspondence to: G. W. Middleton     

Calculation of a gallbladder ejection fraction: advantage of continuous sincalide infusion over the three-minute infusion method.

The purpose of this study was to investigate alternative methods of infusing sincalide for calculation of a gallbladder ejection fraction (GBEF) during cholescintigraphy (5 mCi 99mTc-mebrofenin). After gallbladder filling, three methods of infusion were compared in 23 normal volunteers: (1) 0.02 microgram/kg as a 3-min infusion, (2) 0.02 microgram/kg as a 30-min infusion, and (3) 0.01 microgram/kg as a 30-min infusion (14 subjects), all performed on separate days. With the 3-min infusion, the emptying pattern was usually exponential and completed in 15 min. The mean (GBEF) was 52% +/- 26% at 20 min and 56% +/- 27% at 30 min (range 0%-100%). GBEFs were less than 35% in six subjects and 35%-38% in four. Side effects were noted by 11/23 subjects. With the slow infusions, emptying was linear; no side effects were noted. With 0.02 microgram/kg, the mean GBEF was 50% +/- 27% at 20 min and 70% +/- 22% at 30 min (range 26%-95%). Similar results were seen with 0.01 microgram/kg, but the data were more limited. The 30-min infusion had a higher normalcy rate than the 3-min method (91% versus 74%). Females had significantly lower GBEFs than males (p less than 0.05%). We conclude that the slow infusion method is preferable; it is more physiological, results in more complete emptying, has no side effects, has less normal variability, and should improve the specificity of this test. The lower mean female GBEF may have pathophysiological significance.     

Gorham disease: correlation of MR findings with histopathologic changes

Gorham disease is a rare disorder of unknown etiology characterized by bone destruction and abnormal proliferation of thin-walled vascular channels including lymphatic capillaries. Starting monocentrically in a single bone, the angiomatous masses in this disease extend to adjacent bones and soft tissues without respecting articular barriers. Herein we report a case of Gorham disease with its MR and histopathologic appearance. Received 26 May 1997; Revised 8 October 1997; Accepted 17 February 1998